...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >RIVASTIGMINE IMPROVES HIPPOCAMPAL NEUROGENESIS AND DEPRESSION-LIKE BEHAVIORS VIA 5-HT_(1A) RECEPTOR STIMULATION IN OLFACTORY BULBECTOMIZED MICE
【24h】

RIVASTIGMINE IMPROVES HIPPOCAMPAL NEUROGENESIS AND DEPRESSION-LIKE BEHAVIORS VIA 5-HT_(1A) RECEPTOR STIMULATION IN OLFACTORY BULBECTOMIZED MICE

机译：利福斯汀通过5-HT_（1A）受体刺激刺激造血模型小鼠改善海马神经发生和类似抑郁的行为。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Rivastigmine is a non-competitive inhibitor of both acetylcholinesterase (AChE) and butylcholinesterase (BuChE) used to treat mild to moderate dementia in Alzheimer's disease (AD) patients. Although rivastigmine reportedly ameliorates cognitive dysfunction in these patients, its ability to improve Behavioral and Psychological Symptoms of Dementia (BPSD) remains unclear. To determine whether rivastigmine treatment antagonizes depression-like behaviors, we chronically administered rivastigmine (0.1-1.0 mg/kg) to olfactory bulbectomized (OBX) mice once a day for 2 weeks, starting 2 weeks after bulbectomy. Chronic treatment at 0.3 or 1.0 mg/kg dose dependently and significantly improved depression-like behaviors, as assessed by tail suspension (TST), forced swim (FST), locomotion and novelty-suppressed feeding (NSFT) tests. Importantly, co-administration with WAY-100635 (1.0 mg/kg), a 5-HT_(1A) receptor antagonist, but not ketanserin (1.0 mg/kg,), a 5-HT_(2A) receptor antagonist, completely blocked rivastigmine-induced anti-depressive effects, suggesting that 5-HT_(1A) receptor stimulation mediates this activity. Consistent with this observation, rivastigmine treatment significantly rescued impaired neurogenesis observed in OBX mice in a 5-HT_(1A) receptor-dependent manner. Furthermore, enhanced protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation seen following rivastigmine treatment was closely associated with improved neurogenesis. These effects were blocked by WAY-100635 but not ketanserin treatment. Finally, we confirmed that 5-HT_(1A) but not 5-HT_(2A) receptor stimulation by specific agonists mimicked rivastigmine-induced anti-depression activity and promoted hippocampal neurogenesis. We conclude that, in addition to enhancing the cholinergic system, rivastigmine treatment restores normal function of the hippocampal serotonergic system, an activity that likely ameliorates depressive behaviors in AD patients.
机译：Rivastigmine是乙酰胆碱酯酶（AChE）和丁基胆碱酯酶（BuChE）的非竞争性抑制剂，用于治疗阿尔茨海默病（AD）患者的轻度至中度痴呆。尽管据报道卡巴拉汀可改善这些患者的认知功能障碍，但其改善痴呆的行为和心理症状（BPSD）的能力仍不清楚。为了确定利伐斯的明治疗是否能拮抗抑郁症样的行为，我们从球根切除术后的两周开始，每天一次向嗅觉性球囊切除的（OBX）小鼠施用利伐斯的明（0.1-1.0 mg / kg），持续2周。通过尾部悬吊（TST），强迫游泳（FST），运动和新奇抑制喂养（NSFT）测试评估，以0.3或1.0 mg / kg剂量进行的长期治疗具有依赖性，并显着改善了抑郁症样行为。重要的是，与5-HT_（1A）受体拮抗剂WAY-100635（1.0 mg / kg）共同给药，但与5-HT_（2A）受体拮抗剂酮色林（1.0 mg / kg）共同给药完全阻断了利凡斯的明诱导的抗抑郁作用，提示5-HT_（1A）受体刺激介导了这种活性。与该观察结果一致，利凡斯的明治疗以5-HT_（1A）受体依赖性方式显着拯救了在OBX小鼠中观察到的神经发生受损。此外，在卡巴拉汀治疗后观察到增强的蛋白激酶B（Akt）和细胞外信号调节激酶（ERK）磷酸化与神经发生的改善密切相关。这些作用被WAY-100635阻滞，但酮色林则没有。最后，我们证实了特定激动剂对5-HT_（1A）而非5-HT_（2A）受体的刺激模拟了利凡斯的明诱导的抗抑郁活性并促进了海马神经发生。我们得出的结论是，除增强胆碱能系统外，利凡斯的明治疗还可以恢复海马血清素能系统的正常功能，这种活性可能会改善AD患者的抑郁行为。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号